From Energy Metabolism to Disease: The Multifaceted Roles of Mitochondria

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 31 March 2026 | Viewed by 1113

Special Issue Editors


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Guest Editor
Inflammation & Immunity, Cleveland Clinic, Cleveland, OH, USA
Interests: asthma; chronic obstructive pulmonary disease (COPD); end-stage lung disease

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Guest Editor
Inflammation & Immunity, Cleveland Clinic, Cleveland, OH, USA
Interests: mitochondrial oxidation; dysfunction and cataplerosis; mitochondrial fission and fusion

Special Issue Information

Dear Colleagues,

The mitochondria are motile organelles having metabolic flexibility, which can adapt to energy requirements, stress stimulus, and to the maintenance of an invariable steady-state internal microenvironment. They are metabolic factories that participate in a wide range of significant activities, such as ATP synthesis, fatty acid oxidation, oxidative phosphorylation, calcium regulation, thermal regulation, and ROS generation. However, it is also important to note that the mitochondrial ROS are signaling molecules in immune defense, particularly in inflammatory pathways. Mitochondrial impairment has been related to many diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Most mitochondrial disorders are caused by mutations in mitochondrial DNA, or errors that disturb the delicate play of actions of the hundreds of proteins that are necessary to carry out mitochondrial structure and function, which are present throughout the body (and the body's primary energy source). Symptoms may also differ in type and severity based on the location in the body where the abnormal mitochondria are found and what organs are affected. These include organs with high energy demands, like the brain, heart, muscles, and sensory organs. Muscle weakness, neurologic impairment, sensory loss, heart failure, diabetes, and growth failure are common clinical phenotypes. An understanding of mitochondrial biology is important in the development of therapeutics for these polygenic systemic diseases.

Dr. Amy H. Attaway
Dr. Saurabh Mishra
Guest Editors

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Keywords

  • mitochondrial oxidation
  • ROS
  • aging
  • disease

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Published Papers (1 paper)

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Review

13 pages, 1437 KB  
Review
HPV Oncoproteins and Mitochondrial Reprogramming: The Central Role of ROMO1 in Oxidative Stress and Metabolic Shifts
by Eva Tsoneva and Angel Yordanov
Cells 2025, 14(20), 1629; https://doi.org/10.3390/cells14201629 - 19 Oct 2025
Viewed by 948
Abstract
High-risk human papillomaviruses (HPVs), particularly types 16 and 18, drive carcinogenesis by rewiring host metabolism and mitochondrial function. The oncoproteins E5, E6, and E7 collectively induce mitochondrial fragmentation, increase reactive oxygen species (ROS), and promote a metabolic shift from oxidative phosphorylation (OXPHOS) to [...] Read more.
High-risk human papillomaviruses (HPVs), particularly types 16 and 18, drive carcinogenesis by rewiring host metabolism and mitochondrial function. The oncoproteins E5, E6, and E7 collectively induce mitochondrial fragmentation, increase reactive oxygen species (ROS), and promote a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis (the Warburg effect). A redox-sensitive mitochondrial protein, Reactive Oxygen Species Modulator 1 (ROMO1), has emerged as a key mediator of these processes. ROMO1 contributes to mitochondrial morphology, regulates ROS homeostasis, and interacts with key stress-response pathways. While ROMO1 is overexpressed in many cancers and correlates with poor prognosis, recent data suggest that HPV-associated cervical lesions exhibit a unique biphasic expression pattern, with high ROMO1 levels in early stages and reduced expression in advanced tumors. The underlying molecular mechanisms remain unclear, but may involve HPV genome integration, NF-κB suppression, or epigenetic silencing. Key mechanisms such as how HPV modulates ROMO1 expression and how this contributes to stage-dependent metabolic vulnerability remain incompletely understood. This review highlights the current understanding of how HPV oncoproteins impact mitochondrial structure and function, emphasizes the role of ROMO1 in this context, and compares findings with other cancer types. Although no ROMO1-targeted therapies currently exist, the protein may serve as a redox-sensitive biomarker and potential vulnerability in HPV-driven tumors. We propose that targeting mitochondrial fragmentation, ROS signaling, or metabolic reprogramming may offer new avenues for therapeutic intervention. Further research is needed to clarify ROMO1’s dual role in early vs. late-stage disease and to validate its relevance as a clinical target. Our review fills a gap in the current literature by being the first to systematically explore ROMO1’s contribution to HPV-induced mitochondrial dysfunction and metabolic rewiring, and we outline research priorities for future studies. Full article
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